Synthesis, identification, and biological activity of metabolites of two novel selective S1P1 agonists

被引：9
作者：
Xiao, Qiong [1 ,2 ,3 ,4 ]
Jin, Jing [1 ,2 ]
Wang, Xiaojian [1 ,2 ,3 ,4 ]
Hu, Jinping [1 ,2 ]
Xi, Meiyang [1 ,2 ,3 ,4 ]
Tian, Yulin [1 ,2 ,3 ,4 ]
Yin, Dali [1 ,2 ,3 ,4 ]
机构：
[1] Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
[2] Chinese Acad Med Sci, Beijing 100050, Peoples R China
[3] Inst Mat Med, Beijing Key Lab Act Subst Discovery & Druggabil E, Dept Med Chem, Beijing 100050, Peoples R China
[4] Peking Union Med Coll, Beijing 100050, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2016年 / 24卷 / 10期
基金：
中国国家自然科学基金;
关键词：
S1P(1); Metabolites; Monohydroxylated products; SPHINGOSINE; 1-PHOSPHATE; RECEPTOR; FTY720; AGENT;
D O I：
10.1016/j.bmc.2016.03.059
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
SYL927 and SYL930 are selective S1P(1) agonists under preclinical development. However, during their pharmacokinetic studies we detected two metabolites in rat blood that were tentatively identified as monohydroxylated metabolites of SYL927 and SYL930 based on LC-MS/MS data. In this study, we designed and synthesized possible monohydroxylated products 6a-e and used them as references to confirm the structures of the two metabolites detected by LC-MS/MS. We also evaluated the in vitro and in vivo biological activities of these two metabolites. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2273 / 2279
页数：7
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